Method for preparation of ruthenium-based metathesis catalysts with chelating alkylidene ligands

ABSTRACT

The invention relates to a method for preparation of ruthenium-based carbene catalysts with a chelating alkylidene ligand (“Hoveyda-type catalysts”) by reacting a penta coordinated ruthenium (II)-alkylidene complex of the type (1) (Py)X1X2Ru(alkylidene) with a suitable olefin derivative in a cross metathesis reaction. The method delivers high yields and is conducted preferably in aromatic hydrocarbon solvents. The use of phosphine-containing Ru carbene complexes as starting materials can be avoided. Catalyst products with high purity, particularly with low Cu content, can be obtained.

The present invention relates to a method for the preparation ofruthenium based metathesis catalysts, in particular to the synthesis ofruthenium catalysts, which comprise a chelating alkylidene (carbene)ligand. The method disclosed herein is based on the use of apenta-coordinated Rualkylidene complex as starting material for thesynthesis via a cross metathesis reaction (CM), The preparation methodof the present invention is simple, straightforward, economic& anduseful for industrial scale.

Olefin metathesis is a fundamental catalytic reaction and one of themost versatile ways to break and create new carbon-carbon bonds andbuild molecules. Various general metathesis reaction pathways have beendescribed, such as ring-closing metathesis (RCM), ring-openingmetathesis polymerization (ROMP), cross metathesis (CM) and theircombinations. In the past years, olefin metathesis has become a widelyused method for the formation of carbon-carbon bonds in organicsynthesis and polymer chemistry.

The development of well-defined molydenum-based carbene catalysts bySchrock and ruthenium-based carbene catalysts by Grubbs has led to afast growth in the field of metathesis, particularly for industrialapplications.

The Grubbs “first generation” catalyst, a ruthenium benzylidene complexbearing two tricyclohexylphosphine ligands, having the structure(PCy₃)₂Cl₂Ru═CHPh, was one of the first metathesis catalyst widely usedin organic synthesis. This class of catalysts was followed by a moreactive “second generation” analog, in which N-heterocyclic carbene (NHC)ligands, such as “unsaturated” IMes (=1,3-dimesityl-imidazol-2-ylidene)or “saturated” S-IMes (=H₂IMes 1,3-dimesitylimidazolidine-2-ylidene)replaces one phosphine ligand.

Recently, the so-called “boomerang” catalysts are gaining more and moreattention, Hoveyda et al. prepared latent metathesis catalystscomprising a benzylidene-ether fragment connected to an alkylidene(carbene) moiety (ref to S. B. Garber, J. S. Kingsbury, B. L. Gray, A.H. Hoveyda, Amer. Chem. Soc. 2000, 122, 8168-8179) and WO 02/14376A2.These new type of Ru-catalysts comprise chelating alkylidene ligands(typically alkoxy-benzylidene ligands) and either a PCy₃ (firstgeneration) or NHC (second generation) group.

Over the past years, different types of “boomerang catalysts” weredisclosed in the literature, Examples from the state of the art areRu-complexes comprising a cyclic alkoxybenzylidene ligand with anadditional ester group (ref to WO 2005/016944A1) or an additional ketogroup (ref to WO 2008/034552A1), Furthermore, cyclic chelating Rucomplexes comprising quinoline and quinoxaline derivates are describedin WO 2007/140954. WO 2008/065187A1 discloses cyclic Ru carbenecomplexes with amido-substituted alkoxybenzylidene ligands, WO2004/035596 describes a similar complex bearing an alkoxybenzylideneligand with a nitro-group,

Such “boomerang-type” or “Hoveyda-type” Ru carbene catalysts exhibit abroad application profile in metathesis reactions and may allow for aconsiderable reduction of the catalyst loading In some applications.Additionally, for some systems recyclability has been described,Therefore, these catalysts are gaining increased importance incommercial applications. Consequently, robust and simple manufacturingpathways for these materials are required, which allow production inIndustrial scale.

The general preparation route for chelating “Hoveyda-type” Ru carbenecomplexes is based on the use of ruthenium carbene complexes of the typeX₂L′L″Ru═CHPh (wherein at least one L′ or L″ is a phosphine of the typePR₃) as precursors. These compounds are reacted with suitable olefinicprecursor ligands which comprise an additional donor group. The newcarbene bond is generated by cross metathesis reaction (“CM”), while onephosphine ligand (L′ or L″) is replaced by the donor group of theolefinic ligand, thus forming a chelating ring complex.

U.S. Pat. No. 7,205,424 teaches the preparation of ruthenium-basedolefin metathesis catalysts by a cross metathesis reaction usingRu-indenylidene carbene complexes and an olefin. However, thepreparation of Ru-complexes with chelating alkylidene ligands is notdisclosed.

S. Blechert et al. (Synlett 2001, No 3, 430-432) report the use of a NHCand PPh₃-substituted Ru-indenylidene complex as a precursor for thepreparation of a chelating Ru-alkoyxbenzylidene catalyst (“Hoveyda-type”catalyst) by ring closing metathesis. However, due to the low yieldsreported (i.e. about 40%), this method seems not to be economical.

The use of pyridine-substituted ruthenium carbene complexes asprecursors for the synthesis of Ru carbene catalysts via crossmetathesis (CM) is described in the literature.

A. Hejl, M. W. Day and R. H. Grubbs (Organometallics 2006, 25,6149-6154) describe the preparation of two ruthenium alkylidenecomplexes comprising an imine donor bonded to the alkylidene moiety.These compounds were prepared starting from a hexa-coordinated rutheniumprecursor complex (H₂-IMes)(py)₂Cl₂Ru═CHPh, comprising two pyridineligands and a benzylidene group. Yields of 78 to 84% were reported.

The same precursor complex is used for the synthesis of a rutheniumalkylidene complex containing a cyclic butenyl-pyridyl ligand (T. Ung,A. Heyl, R. H. Grubbs and Y. Schrodi, Organometallics 2004, 23,5399-5401).

WO2007/140954 discloses the use of a 3-bromo-pyridine substitutedcomplex (H₂-IMes)(Br-py)₂Cl₂Ru═CHPh as starting material, again bearingtwo pyridine-type ligands.

M. Barbasievicz et al, report the synthesis of chelating rutheniumquinoline and quinoxaline complexes starting from the benzylidenecompound (H₂-IMes)(PCy₃)Cl₂Ru═CHPh and using Cu(I)Cl as phosphinescavenger (ref to Organometallics 2006, 25(15), 3599-3604).

Hazardous chemicals, such as diazo reagents (e.g. diazoalkenes) arecommonly used in the preparation of ruthenium benzylidene complexes.Therefore, synthesis routes starting from such compounds should beavoided in industrial catalyst production,

It was an objective of the present invention to provide an improvedmethod for preparation of ruthenium-based carbene catalysts withchelating alkylidene ligands (“boomerang-type” catalysts). The newmethod should provide high yields and should not require the use ofhazardous chemicals. Furthermore, the method should provide theruthenium carbene catalysts in high product purity and withoutcontamination (for example without residues of phosphine ligands or Cuions). The method should be easily scalable, environmentally friendlyand applicable at industrial production scale.

The present invention is directed to these objectives by providing themethod according to claim I and the subsequent claims dependent thereon.

According to the present invention, ruthenium-based carbene catalystswith a chelating alkylidene ligand are prepared by the reaction of aruthenium alkylidene starting complex with an olefin derivative viacross metathesis reaction (CM). The method of the present inventionemploys a penta-coordinated ruthenium (II)-alkylidene catalyst of thetype (Py)(L)X¹X² Ru(alkylidene) as starting compound, This startingcomplex has the general formula

In this formula, L is a neutral ligand, X¹ and X² are, independentlyfrom each other, inorganic or organic anionic ligands, such as halideanions, pseudohalide anions, hydroxides, acetates, trifluoracetates orcarboxylates and Py stands for an N-heterocyclic two-electron donorligand. Y¹ and Y² are, independently form each other, hydrogen,C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₆-alkylthio, aryl,arylthio, C₁-C₆-alkylsulfonyl or C₁-C₆-alkylsulfinyl. Preferably, Y¹ andY² are taken together to form a ring of the “Indenylidene” typeaccording to the formula

with R³ being hydrogen, a substituted or unsubstituted aryl group or asubstituted or unsubstituted phenyl group. In a preferred embodiment, R³is a substituted or unsubstituted phenyl group. In a further preferredembodiment, the ligand L is a saturated or unsaturated N-heterocycliccarbene ligand (“NHC” ligand) and the Ru(II)-precursor complexes are ofthe type (Py)(NHC)X¹X²Ru(indenylidene) or(Py)(NHC)X¹X²Ru(phenyl-indenylidene).

The present invention provides a method for preparing a ruthenium-basedcarbene catalyst with a chelating alkylidene ligand comprising thereaction of a ruthenium (II)-alkylidene complex with an olefinderivative according to equation (1):

wherein

-   -   L is a neutral ligand, preferably a saturated or unsaturated        N-heterocyclic carbene ligand (“NHC” ligand),    -   X¹ and X² are, independently from each other, inorganic or        organic anionic ligands, such as halide anions, pseudohalide        anions, hydroxides, acetates, trifluoracetates or carboxylates,    -   Y¹ and Y² are, independently form each other, hydrogen,        C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₆-alkylthio,        aryl, arylthio, C₁-C₆-alkylsulfonyl or C₁-C₆-alkylsulfinyl, or        Y¹ and Y² are taken together to form a ring of the indenylidene        type according to the formula

wherein in said formula R³ is hydrogen, a substituted or unsubstitutedaryl group or a substituted or unsubstituted phenyl group,

-   -   Py is an N-heterocyclic two-electron donor ligand,    -   R⁰ and R¹ are, independently from each other, hydrogen,        C₁-C₁₆-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, a phenyl or an        aryl group (which optionally can be substituted),    -   a, b, c and d are, independently from each other, hydrogen,        C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, a phenyl or aryl        group, or an electron withdrawing group (“EWG”), with the        provision that each of a, b, c or d can form a ring with each        other,    -   Z is a heterodonor atom such as oxygen (O), sulphur (S),        nitrogen (N) or a group comprising a heterodonor atom such as        sulfinyl (>S═O),    -   R² is a substituted or unsubstituted hydrocarbon group, such as        alkyl, alkenyl, alkynyl, aryl, alkylamino, alkylthio, a        substituted or unsubstituted keto group such as        —C(R^(a))₂—CO—C(R^(b))₃, a substituted or unsubstituted ester        group such as —C(R^(a))₂—CO—O(R^(c)) (wherein in said groups        R^(a) is hydrogen or C₁-C₁₀-alkyl, R^(b) is hydrogen,        C₁-C₁₀-alkyl, C₁-C₁₀-fluoroalkyl, C₁-C₁₀-alkylamino,        C₁-C₁₀-alkyl ammonium or C₂-C₁₀-alkenyl and R^(c) is        C₁-C₁₀-alkyl, C₁-C₁₀-fluoroalkyl, C₁-C₁₀-alkylamino,        C₁-C₁₀-alkyl ammonium or C₂-C₁₀-alkenyl) and wherein R² and/or Z        may form a ring with d.

In a preferred embodiment, the present invention is directed to a methodfor preparing a ruthenium-based carbene catalyst with a chelatingalkylidene ligand comprising the reaction of a ruthenium (II)-alkylidenecomplex with an olefin derivative according to equation (1), wherein

-   -   L is a saturated H₂IMes (=1,3-dimesityl-imidazolidine-2-ylidene)        or unsaturated IMes (=13-dimesityl-imidazole-2-ylidene) ligand,    -   X¹ and X² are, independently from each other, anionic ligands        such as Cl—, Br—or I—,

Y¹ and Y² are taken together to form a ring of the indenylidene typeaccording to the formula

-   -   wherein R³ is a substituted or unsubstituted phenyl group,    -   Py is a substituted or un-substituted pyridine ligand,    -   Fe and R¹ are, independent from each other, hydrogen or a        C₁-C₁₀-alkyl group,    -   a, b, c and d are, independent from each other, hydrogen,        C₁-C₁₀-alkyl, a phenyl, an aryl group or an electron withdrawing        group    -   (EWG) such as F, Cl, Br, I, —CF₃, —NO₂, —N(H)—CO—CH₃,    -   N(alkyl)—CO—CH₃, —N(H)—CO—CF₃; —N(alkyl)—CO—CF₃, —O₂S-(alkyl),        —O—CO-(alkyl) or —SO₂—N(CH₃)₂,    -   Z is a heterodonor atom such as oxygen (O) or nitrogen (N),    -   R² is a substituted or unsubstituted alkyl group such as —CH₃ or        —CH(CH₃)₂, a substituted or unsubstituted keto group such as        —CH₂—CO—CH₃, —CH₂—CO—C₂H₅, —CH(CH₃)—CO—CH₃ or —CH(CH₃)—CO—C₂H₅,        a substituted or unsubstituted ester group such as        —CH₂—CO—O—CH₃, —CH₂—CO—O—C₂H₅, —CH(CH₃)—CO—O—CH₃ or        —CH(CH₃)—CO—O—C₂H₅ or an amino-group containing ester group such        as —CH(CH₃)—CO—O—C₂H₄—N(CH₃)₂,    -   and wherein R² and/or the heterodonor atom Z and d may form a        ring.

In a further embodiment of the invention, the substituents of the olefinderivative (specifically R² or the heterodonor atom Z and substituent d)may form a ring. In this case, the heterodonor atom Z preferably isnitrogen (N) and Z and d form a ring to build up a quinoline ringsystem, a quinoxaline ring system or an indol ring system,

Generally, Ru(II)-carbene complexes of the type(Py)(L)X¹X²Ru(alkylidene) are used as starting compounds in the methodof the present invention. Preferably, penta-coordinated ruthenium(indenylidene) carbene complexes are employed. The flu-alkylidenecarbene precursors preferably are phosphine free and comprise a “NHC”ligand and a “Py” ligand, Herein, the term “Py” denotes anN-heterocyclic two-electron donor ligand, preferably a substituted orunsubstituted pyridine ligand.

Examples for suitable Py ligands are pyridine, 3-bromo-pyridine or4-methyl pyridine, quinoline or piperidine. Examples for suitable NHCligands (“N-heterocyclic carbene” ligands) are saturated H₂IMes(=1,3-dimesityl-imidazole-2-ylidene) or unsaturated IMes (=1,3-dimesityl-imidazole-2-ylidene).

X¹ and X² are, independently from each other, inorganic or organicanionic (i.e. negatively charged) ligands, such as halide anions,pseudohalide anions, hydroxides, acetates, trifluoracetates orcarboxylates. Examples for suitable anionic ligands X are the halidesCl—, Br— or I—, with Cl— being most preferred.

R³, which is bonded to the indenylidene moiety, stands for hydrogen, asubstituted or unsubstituted aryl or substituted or unsubstituted phenylgroup; preferably, Fe is a substituted or unsubstituted phenyl group.

A particularly preferred starting compound is(Py)(H₂-IMes)Cl₂Ru(3-phenyl-1H-inden-1-ylidene). This complex can beobtained in excellent yields (>90%) in a ligand exchange reactionstarting from (H₂-IMes)(PCy₃)Cl₂Ru(phenyl-indenylidene) with excesspyridine (ref to D. Burtscher, C, Lexer, K. Mereiter, R. Winde, R. Karchand C. Slugovc, J. of Polymer Science; Part A; Polymer Chemistry 2008,Vol. 46, 4630-4635. Other suitable starting complexes can be prepared bythe person skilled in the art by applying similar methods, Due to thegenerally high yields of these Ru starting compounds, the preparationmethod of the present invention is straightforward and economical. Itcan be applied for the preparation of a great variety of ruthenium-basedcarbene catalysts with chelating alkylidene ligands.

In its preferred versions, the method of the present invention avoidsthe use of Ru carbene complexes with phosphine ligands L as startingmaterials. As, in this case, no phosphine ligands L (such as PPh₃ orPCy₃) are present in the starting complex, less side products (such asfree phosphine ligands or phosphine oxides) are produced.

Furthermore, the addition of Cu(I)Cl, frequently used in the prior artas phosphine scavenger in similar cross metathesis processes, is notnecessary. This results in high purity products with a very lowCu-content, Typically, the Cu-content of the Ru catalyst products isless than 10 ppm, preferably less than 5 ppm (as determined by ICP;ICP=inductive coupled plasma). As an additional advantage, due to theabsence of phosphine ligands in the present method, inert reactionconditions (i.e. a protective gas atmosphere) are not required per se.In many cases, depending on the ligands employed, the preparation methodcan be performed under regular air atmosphere or at least undernon-stringent inert conditions.

Surprisingly, the method of the present invention provides excellentoverall yields in the range of 80 to 95%. This may be due to the uniquestructure of the penta-coordinated Ru (II)-alkylidene complex employedas the starting compound. While the bulky ligand L provides sufficientstability during the reaction, the substitution of the Py ligand by theheterodonor atom (or the heterodonor atom comprising) group Z in thechelating alkylidene moiety occurs rapidly and easily, thus theformation of the chelating ring in the cross metathesis (CM) reaction isfacilitated. Consequently, the reaction times are significantlyshortened.

The precursors for the chelating alkylidene ligands (hereinafter called“olefin derivative”) have the following general formula:

In this formula, R⁰ and R¹ are, independent from each other, hydrogen,C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, a phenyl or an aryl group.

The substituents a, b, c and d can be, independent from each other,hydrogen, C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, a phenyl or arylgroup, or an electron withdrawing group (herein abbreviated “EWG”).Hereinafter, under the term EWG, atoms and/or groups are summarized,which have electron-withdrawing properties and which exhibit higherelectronegativity values (EN) compared to hydrogen (H). Examples forsuitable EWGs are the halogen atoms F, Cl, Br, I or the groups —CF₃,—NO₂, —N(H)—CO—CH₃, N(alkyl)—CO—CH₃, —N(H)—CO—CF₃; —N(alkyl)—CO—CF₃,—O₂S-(alkyl), —O—CO-(alkyl) and —SO₂—N(CH₃)₂.

Furthermore, each of the substituents a, b, c or d may form a ring witheach other.

Z is a heterodonor atom such as oxygen (O), sulphur (S), nitrogen (N) ora group comprising a heterodonor atom, such as sulfinyl (>S═O).Preferably, Z is a heterodonor atom such as oxygen (O) or nitrogen (N).

R² is a substituted or unsubstituted hydrocarbon group, such as alkyl,alkenyl, alkynyl, aryl, alkylamino, alkylthio, a substituted orunsubstituted keto group such as —C(R^(a))₂—CO—C(R^(b))₃, a substitutedor unsubstituted ester group such as —C(R^(a))₂—CO—O(R^(c)) (herein insaid groups Ra is hydrogen or C₁-C₁₀-alkyl, R^(b) is hydrogen,C₁-C₁₀-alkyl, C₁-C₁₀-alkyl ammonium or C₂-C₁₀-alkenyl and R^(c) isC₁-C₁₀-alkyl, C₁-C₁₀-alkylamino, C₁-C₁₀-alkyl ammonium orC₂-C₁₀-alkenyl) and wherein R² and/or Z may form a ring with d.

In general, the precursor ligands may be prepared according to standardprocedures known from the literature or may be obtained commerciallyfrom various suppliers. Examples of olefin derivatives suitable for themethod of the present invention are(E/Z)-1-Isopropoxy-2-(1-propenyl)-benzene,(E/Z)-1-[2-(1-propen-16yl)-phenoxy]-2-propanone),2-isopropoxy-4-nitro-styrene, 2-isopropoxy-3-vinyl-biphenyl or8-vinyl-quinolin. The vinyl quinoline and vinyl-quinoxaline derivatesare obtainable according to the procedures described in the literature(M. Barbaslevicz et al., ref to above).

Generally, the preparation method of the present invention is conductedin aromatic hydrocarbon solvents or chlorinated hydrocarbon solventssuch as dichlormethane or 1,2-dichloroethane. Aromatic hydrocarbonsolvents such as benzene, toluene or xylene are preferred. The use ofthese aromatic hydrocarbon solvents, in particular toluene, provides inmost cases the additional advantage that the resulting rutheniumcomplexes directly precipitate from the reaction mixture thus enablingeasy isolation and workup procedures.

The starting Ru(II)-compound (Py)(L)X¹X²Ru(alkylidene) is dissolved inthe appropriate solvent and the ligand precursor (olefin derivative) isadded. The molar ratio of ligand precursor vs. Ru-starting complex is inthe range of 2:1, preferably in the range of 1.1:1. A stoichiometricratio of both reactants is particularly preferred,

The reaction temperatures are in the range of 0° C. to 150° C.,preferably in the range of room temperature (20° C.) to 100° C. Thesuitable reaction times depend on the type of olefin derivativeemployed. Typically, the reaction times are in the range from 1 to 8hours, preferably in the range from 1 to 5 hours and most preferred inthe range of 1 to 4 hours.

When using aromatic hydrocarbon solvents (such as benzene, toluene orxylene), in many cases the resulting ruthenium catalyst complexes aresparely soluble and precipitate from the reaction mixture upon coolingand/or solvent reduction. The precipitated products are separated fromthe reaction mixture by conventional separation techniques (filtration,centrifuging etc), washed with non-polar solvents such as n-hexane orn-heptane and/or polar solvents such as diethylether or ethanol. Theproducts may be dried by conventional drying methods.

Due to the high purity of the resulting products, there is no need forfurther purification steps (such as chromatography and the like).However, if necessary, additional purification steps such as columnchromatography (LC, HPLC etc) may be employed. The preparation methodaccording to the present invention is very versatile and useful forindustrial, large scale production of catalysts and can be applied to agreat variety of ruthenium-based carbene catalysts with chelatingalkylidene ligands.

The Ru-carbene catalysts (“Hoveyda-type catalysts”) prepared accordingto the present invention exhibit a broad application profile inmetathesis reactions. The catalyst products can be used in a variety ofmetathesis reactions, for example in ring-closing metathesis (RCM),ring-opening metathesis polymerization (ROMP), cross metathesis (CM),acyclic diem-metathesis-polymerization (ADM ET) and their combinations.

The following examples are intended to describe the invention in moredetail, without limiting the scope of protection.

EXAMPLES General Remarks

The ligand precursors/olefin derivatives employed in the followingexamples are known compounds, having CAS Registry Nos. They can beprepared according to methods published in the literature and/orprocedures known to the person skilled in the art. Details: for(E/Z)-1-Isopropoxy-2-(1-propenyl) benzene: CAS Reg. No. 533934-20-2; for(E/Z)-1-[2-(1-propen-1-yl)-phenoxy]-2-propanone): CAS Reg. No.1014701-63-3; for 2-isopropoxy-4-nitrostyrene: CAS Reg. No. 753031-08-2;for 8-vinylquinoline: CAS Reg. No. 96911-08-9.

Example 1 Preparation of

a) Preparation of Starting Compound:

The starting complex was prepared according to D. Buitscher et al., J.of Polymer Science: Part A: Polymer Chemistry 2008, 46, 4630-4635starting from (H₂-IMes)(PCy₃)Cl₂Ru(phenyl-indenylidene) (metathesiscatalyst M2; Umicore AG & Co KG, Hanau) by stirring with excess pyridine(˜30 equivalents) under inert atmosphere for 30 minutes at roomtemperature, Subsequent addition of the reaction mixture to stirredn-heptane and further stirring for 30 minutes at room temperaturefollowed by cooling the reaction mixture overnight (−27° C.) resulted inthe formation of a brown precipitate. The precipitate was filtered off,washed with n-heptane and dried in vacuum. The compound is obtained in95% yield as an orange-brown, microcrystalline solid.

b) Preparation of

Reaction Equation:

2.5 g catalystDichloro-(3-phenyl-1H-Inden-1-ylidene)-(1,3-dimesityl-4,5-dihydro-imidazol-2-ylidene)-(pyridine)-ruthenium(II),[Umicore M31, Umicore AG & Co KG, Hanau] were dissolved In 30 ml oftoluene and 0.7 g of (E/Z)-1-Isopropoxy-2-(1-propenyl)benzene dissolvedin 10 ml toluene were added. The reaction mixture was stirred for 4hours at 65° C. and then cooled down to room temperature. The mixturewas concentrated under vacuum and a green microcrystalline solidprecipitated.

It was filtered and washed with n-hexane and diethyl ether. Thegreen-yellowish product was dried under vacuum (approx. 12 mbar)overnight and characterized by NMR and elemental analysis. Yield: 1.8 g(87%). The analytical data are in agreement with the published data.

Example 2 Preparation of

Reaction Equation:

3.0 g of Umicore M31[Dichloro-(3-phenyl-1H-inden-1-ylidene)-(1,3-dimesityl-4,5-dihydro-imidazol-2-ylidene)-(pyridine)-ruthenium(H);Umicore AG & Co KG, Hanau, prepared as described in Example 1a)] weredissolved in 50 ml of toluene and 0.80 g of(E/Z)-1-[2-(1-propen-1-yl)-phenoxy]-2-propanone), dissolved in 10 mltoluene were added. The reaction mixture was stirred for 3 hours at 65°C. and then cooled down to room temperature. A green microcrystallinesolid precipitated. It was filtered and washed with n-hexane and diethylether. The green-yellowish product was dried under vacuum overnight andcharacterized by NMR and elemental analysis. Yield: 2.2 g (87%).

Example 3 Preparation of

Reaction Equation:

2.5 g catalyst Umicore M31[Dichloro-(3-phenyl-1H-inden-1-ylidene)-(1,3-dirnesityl-4,5-dihydro-imidazol-2-ylidene)-(pyridine)-ruthenium(II);Umicore AG & Co KG, Hanau, prepared as described in Example 1a)] weredissolved in 30 ml of toluene and 0.8 g of 2-isopropoxy-4-nitrostyrenedissolved in 10 ml toluene were added. The reaction mixture was stirredfor 2 hours at 65° C. and then cooled down to room temperature. Themixture was concentrated under vacuum and a green microcrystalline solidprecipitated. It was filtered and washed with n-hexane and diethylether. The green-yellowish product was dried under vacuum overnight andcharacterized by NMR and elemental analysis. Yield: 1.9 g (85%). Theanalytical data are in agreement with the published data,

Example 4 Preparation of

Reaction Equation:

1.0 g catalyst Umicore M31[Dichloro-(3-phenyl-1H-inden-1-yliden)-(1,3-dimesityl-4,5-dihydro-imidazol-2-yliden)-(pyridine)-ruthenium(II)](Umicore AG & Co KG, Hanau) were dissolved in 20 ml of toluene and 0.24g of 8-vinylquinoline dissolved in 5 ml toluene were added. The reactionmixture was stirred for 2 hours at 65° C. and then cooled down to roomtemperature. The mixture was concentrated under vacuum and a greenmicro-crystalline solid precipitated. It was filtered and washed withcold n-hexane and diethyl ether. The green-yellowish product was driedunder vacuum overnight and characterized by NMR and elemental analysis.Yield: 0.7 g (85%), The analytical data are in agreement with thepublished data,

Comparative Example (CE1) Preparation of

via (H₂IMes)(PCy₃)Cl₂Ru(phenylidenylidene) Reaction Equation:

1.15 g (1.2 mmol) of (H₂-IMes)(PCy₃)Cl₂Ru(phenylindenylidene) (UmicoreM2, Umicore AG & Co KG, Hanau) was dissolved in 30 ml of toluene and0.25 g (1.44 mmol, 1.2 eq.) of (E/Z)-1-Isopropoxy-2-(1-propenyl)benzene,dissolved in 10 ml toluene, were added. The reaction mixture was stirredfor 6 hours at 65° C. and then cooled down to room temperature. Themixture was concentrated under vacuum to about 15 ml.

Then, 60 ml of pentane were added under stirring. The resultinggreenish-brown precipitate was separated by filtration and washed withcold pentane and ethyl acetate. The crude product was suspended in 15 mltoluene, filtered and washed with diethyl ether, The green solid wasfinally dried overnight under vacuum. A yield of 0.25 g (30%) wasobtained.

This yield is significantly lower than the yield obtained by the methodaccording to the invention (ref. to Example 1). Furthermore, due to thepresence of a phosphine ligand, additional time-consuming purificationsteps are necessary and the product purity is reduced.

1. Method for the preparation of a ruthenium-based carbene catalyst witha chelating alkylidene ligand comprising the reaction of a ruthenium(II)-alkylidene complex with an olefin derivative according to theequation:

 wherein L is a neutral ligand, preferably a saturated or unsaturatedN-heterocyclic carbene ligand (“NEC” ligand), X¹ and X² are,independently from each other, inorganic or organic anionic ligands,such as halide anions, pseudohalide anions, hydroxides, acetates,trifluoracetates or carboxylates, Y¹ and Y² are, independently -formfrom each other, hydrogen, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,C₁-C₆-alkylthio, aryl, arylthio, C₁-C₆-alkylsulfonyl orC₁-C₆-alkylsulfinyl, or Y¹ and Y² are taken together to form a ring ofthe indenylidene type according to the formula

 wherein in said formula R³ is hydrogen, a substituted or unsubstitutedaryl group or a substituted or unsubstituted phenyl group, Py is anN-heterocyclic two-electron donor ligand, R⁰ and R¹ are, independentlyfrom each other, hydrogen, C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl,a phenyl or an aryl group (which optionally can be substituted), a, b, cand d are, independently from each other, hydrogen, (C₁-C₁₀-alkyl,C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, a phenyl or aryl group, or an electronwithdrawing group (“EWG”), with the provision that each of a, b, c or dcan form a ring with each other, Z is a heterodonor atom such as oxygen(O), sulphur (S), nitrogen (N) or a group comprising a heterodonor atomsuch as sulfinyl (>S═O), R² is a substituted or unsubstitutedhydrocarbon group, such as alkyl, alkenyl, alkynyl, aryl, alkylamino,alkylthio, a substituted or unsubstituted keto group such as—C(R^(a))₂—CO—C(R^(b))₃, a substituted or unsubstituted ester group suchas —C(R^(a))₂—CO—O(R^(c)) (wherein in said groups le is hydrogen orC₁-C₁₀-alkyl, R^(b) is hydrogen, C₁-C₁₀-alkyl, C₁-C₁₀-fluoroalkyl,C₁-C₁₀-alkylamino, C₁-C₁₀-alkyl ammonium or C₂-C₁₀-alkenyl and R^(c) isC₁-C₁₀-alkyl, C₁-C₁₀-fluoroalkyl, C₁-C₁₀-alkyl ammonium orC₂-C₁₀-alkenyl) and wherein R² and/or Z may form a ring with d.
 2. Themethod according to claim 1, wherein L is a saturated H₂IMes(=1,3-dimesityl-imidazolidine-2-ylidene) or unsaturated IMes(=3-dimesityl-imidazole-2-ylidene) ligand, X¹ and X² are, independentlyfrom each other, anionic ligands such as Cl—, Br— or I—, Y¹ and Y² aretaken together to form a ring of the indenylidene type according to theformula

 wherein R³ is a substituted or unsubstituted phenyl group, Py is asubstituted or un-substituted pyridine ligand R⁰ and R¹ are,independently from each other, hydrogen or a C₁-C₁₀-alkyl group, b, cand d are, independently from each other, hydrogen, C₁-C₁₀-alkyl, aphenyl, an aryl group or an electron withdrawing group (EWG) such as F,CI, Br, I, —CF₃, —NO₂, —N(H)CO—CH, —N(alkyl)—CO—CH₃, —N(H)—CO—CF₃;—N(alkyl)—CO—CF₃, —O₂S-(alkyl), —O—CO-(alkyl) or —SO₂—N(CH₃)₂, Z is aheterodonor atom such as oxygen (0) or nitrogen (N), R² is a substitutedor unsubstituted alkyl group such as —CH₃ or —CH(CH₃)₂, a substituted orunsubstituted keto group such as —CH₂—CO—CH₃, —CH₂—CO—C₂H₅,—CH(CH₃)—CO—CH₃ or —CH(CH₃)—CO—C₂H₅, a substituted or unsubstitutedester group such as —CH₂—CO—O—CH₃, —CH₂—CO—O—C₂H₅, —CH(CH₃)—CO—O—CH₃ or—CH(CH₃)—CO—O—C₂H₅ or an amino-group containing ester group such as—CH(CH₃)—CO—O—C₂H₄-N(CH₃)₂, and wherein R² and/or the heterodonor atom Zmay form a ring with d,
 3. The method according to claim 1, wherein thereaction is a cross metathesis reaction (CM).
 4. The method according toclaim 1, wherein the reaction is conducted in aromatic hydrocarbonsolvents.
 5. The method according to claim 1, wherein the reactiontemperature is in the range of 20 to 100° C.
 6. The method according toclaim 1, wherein the molar ratio of olefinic derivative vs. ruthenium(II)-alkylidene complex is in the range of 2:1, preferably in the rangeof 1.1:1.
 7. The method according to claim 1, wherein the reaction timeis in the range of 1 to 8 hours, preferably in the range of 1 to 4hours.
 8. The method according to claim 1, wherein the olefin derivativeis selected from (E/Z)-I-Isopropoxy-2-(1-propenyl)-benzene,(E/Z)-1-[2-(1-propen-1-yl)-phenoxy]-2-propanone),2-isopropoxy-4-nitro-styrene, 8-vinylquinolin or2-isopropoxy-3-vinyl-biphenyl.
 9. The method according to claim 1,further comprising the separation of the ruthenium-based carbenecatalyst with a chelating alkylidene ligand from the reaction mixture byprecipitation and filtration.
 10. Ruthenium-based carbene catalyst witha chelating alkylidene ligand, obtained by the method according to claim1, wherein the Cu content is <10 ppm (as determined by ICP).